The long-term goal of this project is to determine the onset of expression, function and mechanisms of regulation of adhesion receptors in peri- implantation mammalian development. Previous studies by our laboratories have shown that the cadherin and beta-1 integrin families of calcium- dependent cell-cell and cell-matrix adhesion receptors play important roles in morphogenetic events both within the embryo and in interactions between the embryo and extracellular matrix (ECM). Very recent localization studies indicate that cell surface proteoglycans may also be an important class of cell-ECM adhesion receptor during peri-implantation development. The proposed study will focus on the role of the integrin and cell surface proteoglycan classes of cell-ECM adhesion receptors in early mouse development and in embryo implantation as follows. 1) Heterodimer-specific antibodies will be made against individual members of the beta-1 and beta-3 families of integrin adhesion receptors. These will be used to determine the onset and developmental pattern of expression of individual integrin cell-matrix adhesion receptors during peri-implantation mouse development. Oligonucleotides representing subunit specific sequences will be synthesized and used as primer pairs in the reverse transcription-protease chain reaction (RT-PCR) in order to determine the onset of expression of integrin mRNAs. This approach will be complemented by in situ hybridization. 2) Localization studies of the cell surface proteoglycan syndecan will continue. RT-PCR and in situ hybridization will be used to determine the onset and pattern of expression of syndecan mRNA. Syndecan will be characterized biochemically during the course of pre- and peri- implantation development, in order to determine whether the pattern of glycosylation of this hybrid proteoglycan is developmentally regulated. 3) In vitro models for studying ectoplacental cone differentiation, gastrulation and blastocyst interactions with uterine epithelium and underlying matrix will be established. Short peptides containing the arg- gly-asp cell recognition sequence, antibodies made against individual integrins which have functional activity, and existing functional antibodies against syndecan will be used to perturb adhesive interactions in these models. 4) In collaborative experiments, localization, antibody perturbation and RT-PCR studies will be carried out on albino and oligosyndactally mutant embryos and on adrogenote and parthenote embryos. These comparative experiments should shed light on whether the expression or distribution of adhesion receptors is affected in these abnormal embryos. The events to be studied are vital for successful early morphogenesis and implantation and should increase insight into problems relating infertility and embryo wastage as well as contraception. Since these very events cannot be studied in the human, the mouse, which also forms a hemochorial placenta, constitutes an important model system for studying the processes of early embryo morphogenesis and embryo implantation.